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Snail acetylation by autophagy-derived acetyl-coenzyme A promotes invasion and metastasis of KRAS-LKB1 co-mutated lung cancer cells

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Cancer Communications 2022年第8期42卷 716-749页

作者： Jang Hee Han Yong Keon kim Hakhyun kim Jooyoung Lee Myung joon Oh Sang Bum kim Minjee kim Kook Hwan kim Hyun Ju Yoon Myung-Shik Lee John D.Minna Michael A.White Hyun Seok kim Severance Biomedical Science Institute Yonsei University College of MedicineSeoul 03722Korea Department of Medical Science Yonsei University Graduate SchoolSeoul 03722Korea Department of Urology Seoul National University HospitalSeoul 03722Korea Checkmate Therapeutics Inc. Seoul 07207Korea Hamon Center for Therapeutic Oncology Research University of Texas Southwestern Medical CenterDallasTexas 75390USA Department of Cell Biology University of Texas Southwestern Medical CenterDallasTexas 75390USA Graduate School of Medical Science Brain Korea 21 ProjectYonsei University College of MedicineSeoul 03722Korea

Background: Autophagy is elevated in metastatic tumors and is often associatedwith active epithelial-to-mesenchymal transition (EMT). However, the extent towhich EMT is dependent on autophagy is largely unknown. This study aimed toidentify the mechanisms by which autophagy facilitates ***: We employed a liquid chromatography-based metabolomic approachwith kirsten rat sarcoma viral oncogene (KRAS) and liver kinase B1 (LKB1)gene co-mutated (KL) cells that represent an autophagy/EMT-coactivatedinvasive lung cancer subtype for the identification of metabolites linked to autophagy-driven EMT activation. Molecular mechanisms of autophagy-drivenEMT activation were further investigated by quantitative real-time polymerasechain reaction (qRT-PCR), Western blotting analysis, immunoprecipitation,immunofluorescence staining, and metabolite assays. The effects of chemicaland genetic perturbations on autophagic flux were assessed by two orthogonalapproaches: microtubule-associated protein 1A/1B-light chain 3 (LC3) turnoveranalysis by Western blotting and monomeric red fluorescent protein-greenfluorescent protein (mRFP-GFP)-LC3 tandem fluorescent protein quenchingassay. Transcription factor EB (TFEB) activity was measured by coordinatedlysosomal expression and regulation (CLEAR) motif-driven luciferase reporterassay. Experimental metastasis (tail vein injection) mouse models were used toevaluate the impact of calcium/calmodulin-dependent protein kinase kinase 2(CAMKK2) or ATP citrate lyase (ACLY) inhibitors on lung metastasis using IVISluciferase imaging ***: We found that autophagy in KL cancer cells increased acetyl-coenzymeA (acetyl-CoA), which facilitated the acetylation and stabilization of theEMT-inducing transcription factor Snail. The autophagy/acetyl-CoA/acetylSnail axis was further validated in tumor tissues and in autophagy-activatedpancreatic cancer cells. TFEB acetylation in KL cancer cells sustained prometastatic autophagy in a mammalian target o

关键词： snail autophagy acetyl-coenzyme A epithelial-to-mesenchymal transition non-small-cell lung cancer CAMKK2 acetyl-snail pancreatic cancer KRAS inhibitor metastasis ACLY

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Efficacy and safety of newly developed preservative-free latanoprost 0.005% eye drops versus preserved latanoprost 0.005% in open angle glaucoma and ocular hypertension: 12-week results of a randomized,multicenter, controlled phase Ⅲ trial

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International Journal of Ophthalmology(English edition) 2021年第10期14卷 1539-1547页

作者： joon Mo kim Kyung Rim sung Ji Woong Lee Haksu Kyung Seungsoo Rho Chan Yun kim Department of Ophthalmology Kangbuk Samsung HospitalSungkyunkwan University School of MedicineSeoul 03181Republic of Korea Department of Ophthalmology Seoul Asan Medical CenterUlsan University College of MedicineSeoul 05505Republic of Korea Department of Ophthalmology Pusan National University HospitalPusan National University Medical SchoolBusan 49241Republic of Korea Department of Ophthalmology National Medical CenterSeoul 04564Republic of Korea Department of Ophthalmology CHA Bundang Medical CenterCHA UniversitySeongnam 13496Republic of Korea Department of Ophthalmology Severance HospitalYonsei University College of MedicineSeoul 03722Republic of Korea

AIM: To evaluate the therapeutic efficacy, safety and tolerability of newly developed preservative-free(PF) latanoprost generic [TJO-002] and compare it with benzalkonium chloride(BAK)-preserved latanoprost [Xalatan?] in patients with primary open angle glaucoma(POAG) and ocular hypertension(OHT).METHODS: Included patients were aged ≥19 y with POAG/OHT. After a washout period, patients with IOP 21-35 mm Hg at 9 a.m. were enrolled. After a full ophthalmic and glaucoma examination, 144 patients with POAG and OHT participated in this study. Subjects were randomly assigned either PF latanoprost(74 eyes) or BAK-preserved latanoprost(70 eyes). All subjects were examined at 4, 8, and 12 wk after first administration. At each follow-up visit,IOP was measured at 9 a.m. and 5 p.m. and compliance was assessed. Throughout the study, all adverse events were recorded and monitored by the masked investigators who measured ***: Both groups showed a statistically significant decrease of average diurnal IOP at 12 wk compared to baseline(-7.21±3.10 mm Hg in the PF latanoprost group and-7.02±3.17 mm Hg in the BAK latanoprost group, both P<0.0001). There was no statistically significant diurnal IOP variation between the groups. In terms of tolerability, pruritus, burning/stinging, and sticky eye sensation, severity was significantly lower in the PF latanoprost group than in the BAK latanoprost group(P<0.05). CONCLUSION: PF latanoprost has at least similar efficacy in terms of IOP reduction and better tolerability compared with BAK latanoprost.

关键词： latanoprost benzalkonium chloride intraocular pressure preservative-free

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Management of the complications of endoscopic submucosal dissection

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World Journal of Gastroenterology 2011年第31期17卷 3575-3579页

作者： Seong Hwan kim Jeong Seop Moon Young Hoon Youn Ki Myung Lee sung joon Lee Division of Gastroenterology Department of Internal MedicineEulji University Division of Gastroenterology Department of Internal MedicineInje UniversitySeoul Paik Hospital Division of Gastroenterology Department of Internal MedicineYonsei University-ang Nam Severance Hospital Division of Gastroenterology Department of Internal MedicineAjou University Hospital Division of Gastroenterology Department of Internal Medicineang-on University Hospital

Endoscopic submucosal dissection(ESD) is currently widely accepted as a standard treatment option for early gastrointestinal neoplasms in ***,ESD has technical difficulties and a longer procedure time than conventional endoscopic *** it may have a higher risk of complications than conventional endoscopic resection ***,the ESD study group of Korean Society of Gastrointestinal Endoscopy,have experienced many complications,mostly treated by endoscopic or conservative ***,we introduce and share our experiences for managementof post ESD complications and review published papers on the topic.

关键词：并发症内镜管理剥离膜下胃肠道肿瘤治疗方案公共服务

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Optimization of adipose tissue-derived mesenchymal stromal cells transplantation for bone marrow repopulation following irradiation

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World Journal of Stem Cells 2022年第3期14卷 245-263页

作者： Min-Jung kim Won Moon Jeonghoon Heo Sangwook Lim Seung-Hyun Lee Jee-Yeong Jeong Sang joon Lee Department of Biochemistry Cancer Research Institute Kosin University College of MedicineSeo-gu 49267BusanSouth Korea Department of Internal Medicine Kosin University College of MedicineSeo-gu 49267BusanSouth Korea Department of Molecular Biology and Immunology Kosin University College of MedicineSeo-gu 49267BusanSouth Korea Department of Radiation Oncology Kosin University College of MedicineSeo-gu 49267BusanSouth Korea Department of General Surgery Kosin University College of MedicineSeogu 49267BusanSouth Korea Department of Ophthalmology Gospel HospitalKosin University College of MedicineSeo-gu 49267BusanSouth Korea

BACKGROUND Bone marrow(BM)suppression is one of the most common side effects of radiotherapy and the primary cause of death following exposure to *** concerted efforts,there is no definitive treatment method *** studies have reported using mesenchymal stromal cells(MSCs),but their therapeutic effects are *** We administered and examined the effects of various amounts of adipose-derived MSCs(ADSCs)in mice with radiation-induced BM *** Mice were divided into three groups:Normal control group,irradiated(RT)group,and stem cell-treated group following whole-body irradiation(WBI).Mouse ADSCs(mADSCs)were transplanted into the peritoneal cavity either once or three times at 5×10^(5) cells/200μ*** white blood cell count and the levels of,plasma cytokines,BM mRNA,and BM surface markers were compared between the three *** BM-derived CD34+hematopoietic progenitor cells were co-cultured with human ADSCs(hADSCs)or incubated in the presence of hADSCs conditioned media to investigate the effect on human cells in *** The survival rate of mice that received one transplant of mADSCs was higher than that of mice that received three *** transplantations of ADSCs delayed the repopulation of BM hematopoietic stem ***-inflammatory effects and M2 polarization by intraperitoneal ADSCs might suppress erythropoiesis and induce myelopoiesis in sub-lethally RT *** The results suggested that an optimal amount of MSCs could improve survival rates post-WBI.

关键词： Adipose tissue-derived stem cells Bone marrow suppression Mesenchymal stromal cells Radiation Cell therapy

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Identifying the relationships between subsurface absorber defects and the characteristics of kesterite solar cells

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Carbon Energy 2023年第8期5卷 42-54页

作者： Dae-Ho Son Dong-Hwan Jeon Dae-Hwan kim Jin-Kyu Kang Shi-joon sung Jaebaek Lee Taeseon Lee Enkhjargal Enkhbayar JunHo kim Kee-Jeong Yang Division of Energy Technology DGISTDaeguRepublic of Korea Research Center for Thin Film Solar Cells DGISTDaeguRepublic of Korea Department of Physics Incheon National UniversityIncheonRepublic of Korea

Understanding the defect characteristics that occur near the space-charge regions(SCRs)of kesterite(CZTSSe)solar cells is important because the recombination loss at the CZTSSe/CdS interface is considered the main cause of their low *** surfaces with different elemental compositions were formed without polishing(C00)and with polishing for 20 s(C20)and 60 s(C60).For C60,a specific region near the SCR was excessively Cu-rich and Zn-poor compared to C00 and *** charged defects formed where the elemental variation was *** the main deep acceptor defect energy level(E_(a2))near the SCR increased,the efficiency,open-circuit voltage deficit,and current density degraded,and this phenomenon was especially rapid for large E_(a2) *** the E_(a2) near the SCR became deep,the carrier diffusion length decreased more for the CZTSSe solar cells with a low carrier mobility than for the CuInGaSe_(2)(CIGSe)solar *** large amplitude of the electrostatic potential fluctuation in the CZTSSe solar cells induced a high carrier recombination and a short carrier ***,the properties of the CZTSSe solar cells were more strongly degraded by defects with deep energy levels near the SCR than those of the CIGSe solar cells.

关键词： defect density defect energy level elemental variation kesterite space charge region

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On-screen fingerprint sensor with optically and electrically tailored transparent electrode patterns for use on high-resolution mobile displays

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Microsystems & Nanoengineering 2020年第1期6卷 243-254页

作者： Hyun-joon kim-Lee Seog Woo Hong Dong Kyun kim Jinmyoung kim Hong Suk kim Seok-Whan Chung Eun-Hyoung Cho Hae-sung kim Byung-Kyu Lee Device Research Center Samsung Advanced Institute of Technology130 Samsung-roYeongtong-guSuwon-siGyeonggi-do 443-803Republic of Korea

In this study,a mutual capacitive-type on-screen fingerprint sensor,which can recognize fingerprints on a display screen to provide smartphones with full-screen displays with a minimal bezel area,is ***-screen fingerprint sensors are fabricated using an indium tin oxide transparent conductor with a sheet resistance of~10Ω/*** a transmittance of~94%(~86% with the substrate effect)in the visible wavelength range,and assembled onto a display *** at this high transmittance,the electrodes can degrade the display quality when they are placed on the *** interference between periodic display pixel arrays and sensor patterns can lead to the *** is necessary to find an appropriate sensor pattern that minimizes the Moirepattern,while maintaining the signal *** search for appropriate patterns,a numerical calculation is carried out over wide ranges of pitches and rotation *** range is narrowed for an experimental evaluation,which is used to finally determine the sensor *** the selected sensor pitches are too small to detect capacitance variations,three unit patterns are electrically connected to obtain a unit block generating a larger *** applying the selected sensor pattern and circuit driving by block,fingerprint sensing on a display is demonstrated with a prototype built on a commercial smartphone.

关键词： transparent pattern smart

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Acute myeloid leukemia with t(11;19)(q23;p13.1) in a patient with a gastrointestinal stromal tumor undergoing imatinib therapy:A case report

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World Journal of Clinical Cases 2020年第7期8卷 1251-1256页

作者： Hong Jun kim Sun Kyung Baek Chi Hoon Maeng Si-Young kim Tae sung Park Jae joon Han Department of Hematology and Medical Oncology Kyung Hee UniversitySeoul 02447South Korea Department of Laboratory Medicine Kyung Hee UniversitySeoul 02447South Korea

BACKGROUND Acute myeloid leukemia(AML)harboring 11q23 translocations is classified as therapy-related AML in patients who have undergone prior treatment with cytotoxic *** have been only a few reports of AML that subsequently developed during imatinib mesylate(IM)treatment for gastrointestinal stromal tumors(GISTs).CASE SUMMARY A 63-year-old woman was diagnosed with a hepatic GIST recurrence in April 2012;she was administered IM 400 mg/*** November 2015,she developed dyspnea with pancytopenia while IM treatment was continued for 42 mo.A chromosome study using a bone marrow sample showed a 46,XX karyotype with t(11;19)(q23;p13.1)in 22 of 26 analyzed metaphase *** in situ hybridization using the locus-specific indicator(11q23)gene break-apart probe showed positive rearrangement in 82%of interphase ***-transcription polymerase chain reactions subsequently confirmed the KMT2A/ELL *** achieved complete response with incomplete neutrophil recovery with two decitabine treatment *** the third cycle of decitabine,the disease relapsed,and she refused further *** died of hemorrhagic stroke 5 mo after *** the best of our knowledge,this is the first report of AML with KMT2A gene rearrangements in a patient with a GIST receiving IM *** Physicians should consider the potential risks of developing hematologic malignancies,including therapy-related AML,in patients with GISTs receiving IM treatment.

关键词： Acute myeloid leukemia Gastrointestinal stromal tumor Imatinib KMT2A Myelodysplastic syndrome Case report

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Evaluation of the relationship between two different methods for enumeration fecal indicator bacteria: Colony-forming unit and most probable number

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Journal of Environmental Sciences 2010年第6期22卷 846-850页

作者： Kyung Hwa Cho Dukki Han Yongeun Park Seung Won Lee sung Min Cha Joo-Hyon Kang joon Ha kim Department of Environmental Science and Engineering Gwangju Institute of Science and Technology Deparment of Civil and Environmental Engineering Dongguk University-Seoul Sustainable Water Resource Technology Center Gwangju Institute of Science and Technology

Most probable number （MPN） and colony-forming unit （CFU） estimates of fecal indicator bacteria （FIB） concentration are common measures of water quality in aquatic environments. Thus, FIB intensively monitored in Yeongsan Watershed in an attempt to compare two different methods and to develop a statistical model to convert from CFU to MPN estimates or vice versa. As a result, the significant difference was found in the MPN and CFU estimates. The enumerated Escherichia coli concentrations in MPN are greater than those in CFU, except for the measurement in winter. Especially in fall, E. coli concentrations in MPN are one order of magnitude greater than that in CFU. Contrarily, enterococci bacteria in MPN are lower than those in CFU. However, in general, a strongly positive relationship are found between MPN and CFU estimates. Therefore, the statistical models were developed, and showed the reasonable converting FIB concentrations from CFU estimates to MPN estimates. We expect this study will provide preliminary information towards future research on whether different analysis methods may result in different water quality standard violation frequencies for the same water sample.

关键词： most probable number colony-forming unit fecal indicator bacteria Escherichia coli enterococci

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Ultrasonic Approach of Rayleigh Pitch-Catch Contact Ultrasound Waves on CFRP Laminated Composites

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Journal of Materials Science & Technology 2008年第3期24卷 407-409页

作者： In-Young Yang Kwang-Hee Im Uk Heo David K Hsu Je-Woong Park Hak-joon kim sung-Jin Song School of Mechanical Eng. Chosun Univ Department of Automotive Eng. Woosuk Univers-ity Center for Nondestructive Evaluation Iowa State University Dept.of Naval Arch.and Ocean Eng. Chosun Univ School of Mechanical Eng. Sungkyunkwan University

CFRP （carbon fiber reinforced plastics） composite materials have wide applicability because of their inherent design flexibility and improved material properties. However, impacted composite structures have 50%-75% less strength than undamaged structures. In this work, a CFRP composite material was nondestructively characterized in order to ensure product quality and structural integrity of CFRP and one-sided pitch-catch technique was developed to measure impacted-damaged area by using an automated-data acquisition system in an immersion tank. A pitch-catch signal was found to be more sensitive than normal incidence backwall echo of longitudinal wave under defect conditions in the composite.

关键词： Impact damages C-scanner Carbon fiber reinforced plastics (CFRP) Pitchcatch mode

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Graphene electrode with tunable charge transport in thin-film transistors

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Nano Research 2018年第1期11卷 274-286页

作者： Ick-joon Park Tae In kim In-Tak Cho Chang-Woo Song Ji-Woong Yang Hongkeun Park Woo-Seok Cheong sung Gap Im Jong-Ho Lee sung-Yool Choi School of Electrical Engineering GrapheneY2D Materials Research Center Korea Advanced Institute of Science and Technology (KAIST) Daejeon 34141 Republic of Korea Department of Electrical Engineering Seoul National University Seou108826 Republic of Korea Electronics and Telecommunications Research Institute Daejeon 34129 Republic of Korea Department of Chemical and Biomolecular Engineering Graphene/2D Materials Research Center Korea Advanced Institute of Science and Technology (KAIST) Daejeon 34141 Republic of Korea

Graphene, a single atomic layer of sp2-hybridized carbon, has immense potential as a transparent conducting material in electronic applications owing to its superior properties, including optical transparency and high conductivity. Particularly, the tunable work function of graphene enables the integration of graphene electrodes with various electronic devices. To achieve high performance in graphene-based devices, effective charge transport between the graphene electrode and the semiconducting material needs to be optimized; this is closely related to the modulation of the Schottky barrier （SB）. In this study, we investigate the ~nable charge transport properties as a function of graphene doping in n-channel thin-film transistors （TFTs） in terms of the electrical characteristics and low-frequency noise （LFN） behaviors. Alkali metal carbonates tuned the work function of graphene, resulting in a dramatic decrease in the SB and an improvement of the carrier injection in n-channel TFTs. The electrical performance of the TFTs was evaluated by extraction of the field-effect mobilities and ratio of contact resistance to total resistance. Furthermore, the level of contact noise created by the barrier height fluctuation and relative contribution of channel noise and contact noise in the TFTs was investigated by LFN measurements to demonstrate the ~nable charge transport. Our findings therefore provide new insights into the tunable charge transport mechanism in graphene-based devices and reveal the immense potential of graphene as electrodes in high performance flexible and transparent displays.

关键词： charge transport graphene doping Schottky barrier work function contact property low-frequency noise

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